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Fatigue in rheumatoid arthritis; a persistent problem: a large longitudinal study.

van Steenbergen HW, Tsonaka R, Huizinga TW, Boonen A, van der Helm-van Mil AH - RMD Open (2015)

Bottom Line: After multiple imputation, the serial measurements were analysed using linear quantile mixed models.Although improved treatment strategies associated with less severe radiographic progression, there was no effect on fatigue severity (p=0.96).Improved treatment strategies did not result in less severe fatigue.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology , Leiden University Medical Center , Leiden , The Netherlands.

ABSTRACT

Objective: Fatigue is prevalent and disabling in rheumatoid arthritis (RA). Surprisingly, the long-term course of fatigue is studied seldom and it is unclear to what extent it is influenced by inflammation. This study aimed to determine the course of fatigue during 8 years follow-up, its association with the severity of inflammation and the effect of improved treatment strategies.

Methods: 626 patients with RA included in the Leiden Early Arthritis Clinic cohort were studied during 8 years. Fatigue severity, measured on a 0-100 mm scale, and other clinical variables were assessed yearly. Patients included in 1993-1995, 1996-1998 and 1999-2007 were treated with delayed treatment with disease-modifying antirheumatic drugs (DMARDs), early treatment with mild DMARDs and early treatment with methotrexate respectively. After multiple imputation, the serial measurements were analysed using linear quantile mixed models.

Results: Median fatigue severity at baseline was 45 mm and remained, despite treatment, rather stable thereafter. Female gender (effect size=4.4 mm), younger age (0.2 mm less fatigue/year), higher swollen and tender joint counts (0.3 mm and 1.0 mm more fatigue/swollen or tender joint) and C reactive protein-levels (0.1 mm more fatigue per mg/L) were independently and significantly (p<0.05) associated with fatigue severity over 8 years. Although improved treatment strategies associated with less severe radiographic progression, there was no effect on fatigue severity (p=0.96).

Conclusions: This largest longitudinal study on fatigue so far demonstrated that the association between inflammation and fatigue is statistically significant but effect sizes are small, suggesting that non-inflammatory pathways mediate fatigue as well. Improved treatment strategies did not result in less severe fatigue. Therefore, fatigue in RA remains an 'unmet need'.

No MeSH data available.


Related in: MedlinePlus

Fatigue severity across early patients with arthritis with different diagnoses at disease onset (A) and over 3 years of disease (B). (A) Presented are medians and IQRs of fatigue severity at disease onset. The data of rheumatoid arthritis (RA) are presented in bold. An asterisk indicates a significant different fatigue level compared to RA when adjusted for age and gender. The numbers of patients at baseline are 902 for RA, 73 for SCTD, 48 for RS3PE, 96 for reactive arthritis, 19 for paramalignant arthritis, 65 for sarcoidosis, 25 for others, 126 for inflammatory OA, 13 for lyme arthritis, 706 for UA, 271 for PsA/SpA, 90 for (pseudo)gout, four for septic arthritis and four for post-traumatic joint swelling. (B) Presented are medians of fatigue severity over 3 years of disease. Available, unmodelled data without imputation of missing data is depicted. The numbers of available fatigue data per diagnosis at baseline, one, 2 and 3 years follow-up were respectively: 73, 32, 25 and 21 for SCTD; 902, 537, 411 and 432 for RA; 706, 270, 155 and 139 for UA; 271, 151, 110, 101 for PsA/SpA; 90, 13, 4 and 2 for (pseudo)gout. SCTD, systemic connective tissue disease; RS3PE, remitting seronegative symmetrical synovitis with pitting edema; RA, rheumatoid arthritis; OA, osteoarthritis; UA, undifferentiated arthritis; PsA, psoriatic arthritis; SpA, spondylarthropathy with peripheral arthritis.
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RMDOPEN2014000041F1: Fatigue severity across early patients with arthritis with different diagnoses at disease onset (A) and over 3 years of disease (B). (A) Presented are medians and IQRs of fatigue severity at disease onset. The data of rheumatoid arthritis (RA) are presented in bold. An asterisk indicates a significant different fatigue level compared to RA when adjusted for age and gender. The numbers of patients at baseline are 902 for RA, 73 for SCTD, 48 for RS3PE, 96 for reactive arthritis, 19 for paramalignant arthritis, 65 for sarcoidosis, 25 for others, 126 for inflammatory OA, 13 for lyme arthritis, 706 for UA, 271 for PsA/SpA, 90 for (pseudo)gout, four for septic arthritis and four for post-traumatic joint swelling. (B) Presented are medians of fatigue severity over 3 years of disease. Available, unmodelled data without imputation of missing data is depicted. The numbers of available fatigue data per diagnosis at baseline, one, 2 and 3 years follow-up were respectively: 73, 32, 25 and 21 for SCTD; 902, 537, 411 and 432 for RA; 706, 270, 155 and 139 for UA; 271, 151, 110, 101 for PsA/SpA; 90, 13, 4 and 2 for (pseudo)gout. SCTD, systemic connective tissue disease; RS3PE, remitting seronegative symmetrical synovitis with pitting edema; RA, rheumatoid arthritis; OA, osteoarthritis; UA, undifferentiated arthritis; PsA, psoriatic arthritis; SpA, spondylarthropathy with peripheral arthritis.

Mentions: Table 1 presents the characteristics of the studied patients. First, we studied whether the fatigue severity differed between patients presenting with RA and other forms of early arthritis. Of the 2442 patients with fatigue data at disease onset, 902 patients had RA and 1540 patients other diagnoses. Figure 1A presents medians of fatigue severity for different diagnoses. Patients with SCTD and RS3PE recorded significantly more severe fatigue than patients with RA (medians respectively 59 mm and 58 mm compared to 49 mm in RA; p<0.05 adjusted for age and gender). Patient groups that experienced significantly less fatigue than patients with RA were patients with UA (median 37 mm), PsA/SpA (median 30 mm) and septic arthritis (25 mm) (all p<0.05 adjusted for age and gender). Four included patients were finally diagnosed with post-traumatic joint swelling; these patients had a median fatigue severity of zero (figure 1). Evaluating available data on the fatigue course over the first 3 years of disease revealed a similar trend as for the baseline data: patients with SCTD remained more severe fatigued than patients with RA and patients with PsA/SpA and (pseudo)gout had less severe fatigue also during follow-up (figure 1B).


Fatigue in rheumatoid arthritis; a persistent problem: a large longitudinal study.

van Steenbergen HW, Tsonaka R, Huizinga TW, Boonen A, van der Helm-van Mil AH - RMD Open (2015)

Fatigue severity across early patients with arthritis with different diagnoses at disease onset (A) and over 3 years of disease (B). (A) Presented are medians and IQRs of fatigue severity at disease onset. The data of rheumatoid arthritis (RA) are presented in bold. An asterisk indicates a significant different fatigue level compared to RA when adjusted for age and gender. The numbers of patients at baseline are 902 for RA, 73 for SCTD, 48 for RS3PE, 96 for reactive arthritis, 19 for paramalignant arthritis, 65 for sarcoidosis, 25 for others, 126 for inflammatory OA, 13 for lyme arthritis, 706 for UA, 271 for PsA/SpA, 90 for (pseudo)gout, four for septic arthritis and four for post-traumatic joint swelling. (B) Presented are medians of fatigue severity over 3 years of disease. Available, unmodelled data without imputation of missing data is depicted. The numbers of available fatigue data per diagnosis at baseline, one, 2 and 3 years follow-up were respectively: 73, 32, 25 and 21 for SCTD; 902, 537, 411 and 432 for RA; 706, 270, 155 and 139 for UA; 271, 151, 110, 101 for PsA/SpA; 90, 13, 4 and 2 for (pseudo)gout. SCTD, systemic connective tissue disease; RS3PE, remitting seronegative symmetrical synovitis with pitting edema; RA, rheumatoid arthritis; OA, osteoarthritis; UA, undifferentiated arthritis; PsA, psoriatic arthritis; SpA, spondylarthropathy with peripheral arthritis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4612698&req=5

RMDOPEN2014000041F1: Fatigue severity across early patients with arthritis with different diagnoses at disease onset (A) and over 3 years of disease (B). (A) Presented are medians and IQRs of fatigue severity at disease onset. The data of rheumatoid arthritis (RA) are presented in bold. An asterisk indicates a significant different fatigue level compared to RA when adjusted for age and gender. The numbers of patients at baseline are 902 for RA, 73 for SCTD, 48 for RS3PE, 96 for reactive arthritis, 19 for paramalignant arthritis, 65 for sarcoidosis, 25 for others, 126 for inflammatory OA, 13 for lyme arthritis, 706 for UA, 271 for PsA/SpA, 90 for (pseudo)gout, four for septic arthritis and four for post-traumatic joint swelling. (B) Presented are medians of fatigue severity over 3 years of disease. Available, unmodelled data without imputation of missing data is depicted. The numbers of available fatigue data per diagnosis at baseline, one, 2 and 3 years follow-up were respectively: 73, 32, 25 and 21 for SCTD; 902, 537, 411 and 432 for RA; 706, 270, 155 and 139 for UA; 271, 151, 110, 101 for PsA/SpA; 90, 13, 4 and 2 for (pseudo)gout. SCTD, systemic connective tissue disease; RS3PE, remitting seronegative symmetrical synovitis with pitting edema; RA, rheumatoid arthritis; OA, osteoarthritis; UA, undifferentiated arthritis; PsA, psoriatic arthritis; SpA, spondylarthropathy with peripheral arthritis.
Mentions: Table 1 presents the characteristics of the studied patients. First, we studied whether the fatigue severity differed between patients presenting with RA and other forms of early arthritis. Of the 2442 patients with fatigue data at disease onset, 902 patients had RA and 1540 patients other diagnoses. Figure 1A presents medians of fatigue severity for different diagnoses. Patients with SCTD and RS3PE recorded significantly more severe fatigue than patients with RA (medians respectively 59 mm and 58 mm compared to 49 mm in RA; p<0.05 adjusted for age and gender). Patient groups that experienced significantly less fatigue than patients with RA were patients with UA (median 37 mm), PsA/SpA (median 30 mm) and septic arthritis (25 mm) (all p<0.05 adjusted for age and gender). Four included patients were finally diagnosed with post-traumatic joint swelling; these patients had a median fatigue severity of zero (figure 1). Evaluating available data on the fatigue course over the first 3 years of disease revealed a similar trend as for the baseline data: patients with SCTD remained more severe fatigued than patients with RA and patients with PsA/SpA and (pseudo)gout had less severe fatigue also during follow-up (figure 1B).

Bottom Line: After multiple imputation, the serial measurements were analysed using linear quantile mixed models.Although improved treatment strategies associated with less severe radiographic progression, there was no effect on fatigue severity (p=0.96).Improved treatment strategies did not result in less severe fatigue.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology , Leiden University Medical Center , Leiden , The Netherlands.

ABSTRACT

Objective: Fatigue is prevalent and disabling in rheumatoid arthritis (RA). Surprisingly, the long-term course of fatigue is studied seldom and it is unclear to what extent it is influenced by inflammation. This study aimed to determine the course of fatigue during 8 years follow-up, its association with the severity of inflammation and the effect of improved treatment strategies.

Methods: 626 patients with RA included in the Leiden Early Arthritis Clinic cohort were studied during 8 years. Fatigue severity, measured on a 0-100 mm scale, and other clinical variables were assessed yearly. Patients included in 1993-1995, 1996-1998 and 1999-2007 were treated with delayed treatment with disease-modifying antirheumatic drugs (DMARDs), early treatment with mild DMARDs and early treatment with methotrexate respectively. After multiple imputation, the serial measurements were analysed using linear quantile mixed models.

Results: Median fatigue severity at baseline was 45 mm and remained, despite treatment, rather stable thereafter. Female gender (effect size=4.4 mm), younger age (0.2 mm less fatigue/year), higher swollen and tender joint counts (0.3 mm and 1.0 mm more fatigue/swollen or tender joint) and C reactive protein-levels (0.1 mm more fatigue per mg/L) were independently and significantly (p<0.05) associated with fatigue severity over 8 years. Although improved treatment strategies associated with less severe radiographic progression, there was no effect on fatigue severity (p=0.96).

Conclusions: This largest longitudinal study on fatigue so far demonstrated that the association between inflammation and fatigue is statistically significant but effect sizes are small, suggesting that non-inflammatory pathways mediate fatigue as well. Improved treatment strategies did not result in less severe fatigue. Therefore, fatigue in RA remains an 'unmet need'.

No MeSH data available.


Related in: MedlinePlus